Improving the safety of human pluripotent stem cell therapies using genome-edited orthogonal safeguards.

ABSTRACT: Despite their rapidly-expanding therapeutic potential, human pluripotent stem cell (hPSC)-derived cell therapies continue to have serious safety risks. Transplantation of hPSC-derived cell populations into preclinical models has generated teratomas (tumors arising from undifferentiated hPSCs), unwanted tissues, and other types of adverse events. Mitigating these risks is important to increase the safety of such therapies. Here we use genome editing to engineer a general platform to improve the safety of future hPSC-derived cell transplantation therapies. Specifically, we develop hPSC lines bearing two drug-inducible safeguards, which have distinct functionalities and address separate safety concerns. In vitro administration of one small molecule depletes undifferentiated hPSCs >10⁶

SUBMITTER: Martin RM 

PROVIDER: S-EPMC7264334 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature